Targeting the Hippo pathway in cancer

Kieran F. Harvey, Tracy T. Tang
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Abstract

The Hippo pathway is a highly conserved signalling network that controls tissue growth and cell fate, responding to physical properties of the tissue microenvironment and cell biological features such as adhesion and polarity. Hippo signalling perturbation is associated with several human diseases, particularly various solid cancers. Hippo pathway-targeted therapies are beginning to emerge for the treatment of cancer, most of which are focused on disrupting the ability of the YAP and TAZ transcription co-activator proteins to promote transcription of genes with their cognate TEAD1–4 DNA binding proteins. Recently, TEAD inhibitors have shown promise in a phase I clinical trial in cancers that are enriched for Hippo pathway mutations, such as mesothelioma. Moreover, Hippo pathway-targeted therapies have great potential to be combined with RAS–MAPK pathway inhibitors, given the close functional relationship that these signalling pathways share in development and disease.

Abstract Image

靶向癌症中的Hippo通路
Hippo通路是一个高度保守的信号网络,控制组织生长和细胞命运,响应组织微环境的物理特性和细胞生物学特征,如粘附性和极性。河马信号紊乱与几种人类疾病有关,特别是各种实体癌。Hippo通路靶向治疗开始出现,用于治疗癌症,其中大多数集中在破坏YAP和TAZ转录共激活蛋白的能力,以促进与其同源TEAD1-4 DNA结合蛋白的基因转录。最近,TEAD抑制剂在Hippo通路突变富集的癌症(如间皮瘤)的I期临床试验中显示出前景。此外,考虑到这些信号通路在发育和疾病中共享的密切功能关系,Hippo通路靶向治疗与RAS-MAPK通路抑制剂联合具有很大的潜力。
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